Molecular Features and Clinical Management of Hereditary Pancreatic Cancer Syndromes and Familial Pancreatic Cancer.

Abstract

Hereditary pancreatic cancers are caused by several inherited genes. Familial pancreatic cancer is defined as pancreatic cancer arising in a patient with at least two first-degree relatives with pancreatic cancer in the absence of an identified genetic cause. Hereditary pancreatic cancer syndromes and familial pancreatic cancers account for about 10% of pancreatic cancer cases. Germline mutations in BRCA1, BRCA2, ATM, PALB2, CDKN2A, STK11, and TP53 and mismatch repair genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) are among the well-known inherited susceptibility genes. Currently available targeted medications include poly (ADP-ribose) polymerase inhibitors (PARP) for cases with mutant BRCA and immune checkpoint inhibitors for cases with mismatch repair deficiency. Loss of heterozygosity of hereditary pancreatic cancer susceptibility genes such as BRCA1/2 plays a key role in carcinogenesis and sensitivity to PARP inhibitors. Signature 3 identified by whole genome sequencing is also associated with homologous recombination deficiency and sensitivity to targeted therapies. In this review, we summarize molecular features and treatments of hereditary pancreatic cancer syndromes and surveillance procedures for unaffected high-risk cases. We also review transgenic murine models to gain a better understanding of carcinogenesis in hereditary pancreatic cancer.

• Authors: Akiyoshi Kasuga, Takeshi Okamoto, Shohei Udagawa, Chinatsu Mori, Takafumi Mie, Takaaki Furukawa, Yuto Yamada, Tsuyoshi Takeda, Masato Matsuyama, Takashi Sasaki, Masato Ozaka, Arisa Ueki, Naoki Sasahira
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 3 (Jan 21 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35163129 (Publication Type: Journal Article, Review)

Chemical References

• Biomarkers, Tumor

Topics

• Biomarkers, Tumor (genetics)
• Carcinoma (genetics, pathology, therapy)
• Disease Management
• Genetic Predisposition to Disease
• Germ-Line Mutation
• Humans
• Neoplastic Syndromes, Hereditary (genetics, pathology, therapy)
• Pancreatic Neoplasms (genetics, pathology, therapy)